Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons Orchestrates Motor Control
The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs) of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plas...
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Published in | Cell reports (Cambridge) Vol. 13; no. 7; pp. 1353 - 1365 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
17.11.2015
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs) of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson’s disease, we determined the circuit and behavioral effects of concurrently regulating cell-type-specific forms of corticostriatal long-term synaptic depression (LTD) by inhibiting small-conductance Ca2+-activated K+ channels (SKs) of the dorsolateral striatum. At striatopallidal synapses, SK channel inhibition rescued the disease-linked deficits in endocannabinoid (eCB)-dependent LTD. At striatonigral cells, inhibition of these channels counteracted a form of adenosine-mediated LTD by activating the ERK cascade. Interfering with eCB-, adenosine-, and ERK signaling in vivo alleviated motor abnormalities, which supports that synaptic modulation of striatal pathways affects behavior. Thus, our results establish a central role of coordinated synaptic plasticity at MSN subpopulations in motor control.
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•eCBs govern LTD in striatopallidal neurons and adenosine does so in striatonigral cells•Parkinson’s disease (PD)-like dopamine (DA) depletion impairs eCB-, but not adenosine-LTD•DA deficits are circumvented by resuming cell-type-specific eCB and ERK signaling•Segregated modulation of eCB and ERK signaling alleviates PD motor abnormalities
Trusel et al. highlight the motor implications of restoring functional integration of presynaptic and postsynaptic mechanisms of plasticity at striatal projection neurons, by resuming cell-type-specific activation of eCB and ERK signaling in dopamine-depleted mice. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2015.10.009 |